There are several strengths of this study design, the first being the use of families densely affected with alcohol dependent individuals. Family (Merikangas et al., 1998; Nurnberger et al., 2004) and twin (Tsuang et al., 1998) studies suggest familial co-aggregation and heritable overlap across alcohol, cannabis, cocaine and opioids. Thus, this family-based COGA sample, enriched for dependence on multiple substances and shared genetic risk, allowed us to test for the association of common variants with risk for dependence across multiple substances. A second strength of this study was the use of a family-based association design. This allowed us to examine association within a family consisting of members who endorsed criteria for dependence on different (or multiple) substances. Third, family-based analysis is robust to population substructures such as nuanced differences in ethnicity, which might occur with marry-in individuals of a different race, and in turn affects the genetic diversity of the offspring.
